Experience-dependent regulation of adult hippocampal neurogenesis: effects of long-term stimulation and stimulus withdrawal.

Exposure to an enriched environment has been shown to cause an increase in neurogenesis in the dentate gyrus of adult mice. In this study we examined how this experience-dependent response in adult hippocampal neurogenesis of C57BL/6 mice is modulated under the conditions of long-term stimulation and of withdrawal from the enriched environment. We found that a group which experienced withdrawal from the enriched environment 3 months earlier, had more than twice as many proliferating cells in the subgranular zone as controls and mice experiencing long-term stimulation. We propose that the greater number of proliferating cells after withdrawal reflects a survival-promoting effect on the dividing neuronal stem and progenitor cells during the earlier period of stimulation. No differences between the groups were observed in the number of surviving progeny or their phenotypes. Therefore, the existence of more dividing cells in the withdrawal group did not translate into a significant net increase in neurogenesis in the absence of continued stimulation. Similarly, the finding in the group experiencing long-term stimulation showing no clear benefit over controls could be interpreted as a diminished efficiency of continued environmental stimuli to elicit a neurogenic response. Thus, we propose as a working hypothesis that: 1) stimulation early in life may preserve the neurogenic potential in the dentate gyrus, and 2) the novelty of complex stimuli rather than simply continued exposure to complex stimuli elicits the environmental effects on adult hippocampal neurogenesis.